Table 2.

Exposure to antibiotics and health outcomes from selected human studies.

Antibiotic exposure	Type of study	Outcome	Study
Any exposure of lifetime	Population study	An increase risk of Schizophrenia (HR of 1.37 with 95% CI = 1.20–1.57) and affective disorders (HR 1.64 with 95% CI = 1.48–1.82)	(116)
Early life/childhood exposure	Population study	It was found that with any antibiotic exposure there was increased risk of mood disorders and ADHD (HR 1.15 with 95% CI = 1.13–1.17)	(117)
Exposure greater than 1 year from index diagnosis of either 1 of 7 classes of antibiotics	Nested case control study	Study examined patients with depression (N = 202,974), anxiety (N = 14,570), and psychosis (N = 2,690). Those treated with a single antibiotic course has a higher risk for depression with all antibiotic groups with AOR of 1.23 for penicillins (95% CI = 1.18–1.29) and 1.25 (95% CI = 1.15–1.35) for quinolones. There was increased risk with recurrent exposures of 2–5 courses (AOR 1.40 with 95% CI = 1.35–1.46) and > 5 courses (AOR 1.56 CI = 1.46–1.65) of penicillin. With anxiety there was an increased AOR with penicillins and sulfonamides of 1.17 (95% CI – 1.01-1.36) for a single course of penicillin and with >5 courses an AOR of 1.44 (95% CI 1.18–1.75) There was no observed change in risk for psychosis with any antibiotic group.	(118)
Antibiotic exposure either alone or in combination with other antibiotics or medications	Systematic review	There was an increased risk of developing depression by 20% in patients, even 5–10 years after use. Suspected that alteration in the microbiome and diversity was a contributing factor.	(119)
Early life/childhood exposure (within first 2 years of life)	Meta-analysis	Studies included up to 3.5 million children. Found that antibiotic exposure within the first 2 years lead to an increased risk of asthma, eczema, and obesity (p < 0.05). It was found that exposure during the first 6 months being most critical, as this is the time when the microbiome is more susceptible.	(120)
Cumulative antibiotic use of the course of life	Cohort study- NHS	The study looked at 36429 women and antibiotic use in young (20–39), middle (40–59), and late (≥60) adulthood. There was an increased risk of CVD in the late adulthood group with long-term (> 2 months) antibiotic use (HR 1.32, 95% CI 1.03–1.70). As well, longer duration of antibiotic use in middle adulthood group has higher risk of CVD (P trend = 0.003). No risk was observed in the young adult group.	(121)

AOR, adjusted odds ratio; CVD, cardiovascular disease; CI, confidence interval; HR, hazard ratio; NHS, nurses health study.